Brett Cook, Wilson & Feinstein lab, PhD Defense

Speaker

Date and Location

Abstract

Even the best available chemotherapies frequently induce painful and debilitating side effects that interfere with cancer treatment. One such side effect, peripheral neuropathy, is a dose-limiting sensory neurotoxicity that is commonly seen after treatment with agents that combat cancer cell growth by interfering with microtubule dynamics. The onset, rate of progression, and severity of neuropathy vary greatly among the different classes of microtubule targeting agents (MTAs). Given the importance of the microtubule cytoskeleton to sensory neurons and the variability in pathophysiology among MTAs, we hypothesize that each agent’s unique mechanism of microtubule binding and inhibition underlies the variability in neuropathic symptoms. In this seminar I will present the effects associated with the induction and resolution of neuropathy initiated by MTAs in mouse peripheral sciatic nerves using immunofluorescent microscopy. Our findings indicate that each MTA induces unique morphological and biochemical changes to peripheral axons and myelin that resolve at different rates. Additionally, we found that eribulin, an agent with a lower frequency of severe neuropathy, tended to promote biochemical changes associated with microtubule growth and stability. This work provides a molecular rationale for the variability in onset, progression, and severity of neuropathies induced by MTA chemotherapies.